PINK1 deficiency impairs osteoblast differentiation through aberrant mitochondrial homeostasis

Abstract Background PTEN-induced kinase 1 (PINK1) is a serine/threonine-protein kinase in mitochondria that is critical for mitochondrial quality control. PINK1 triggers mitophagy, a selective autophagy of mitochondria, and is involved in mitochondrial regeneration. Although increments of mitochondr...

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Autores principales:	So-Young Lee, Hyun-Ju An, Jin Man Kim, Min-Ji Sung, Do Kyung Kim, Hyung Kyung Kim, Jongbeom Oh, Hye Yun Jeong, Yu Ho Lee, Taeyoung Yang, Jun Han Kim, Ha Jeong Lim, Soonchul Lee
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Mitochondria Osteogenesis Osteoporosis PINK1 Medicine (General) R5-920 Biochemistry QD415-436
Acceso en línea:	https://doaj.org/article/1be6bdaa122f4eaa98fa9e01194789de
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spelling	oai:doaj.org-article:1be6bdaa122f4eaa98fa9e01194789de2021-11-28T12:06:22ZPINK1 deficiency impairs osteoblast differentiation through aberrant mitochondrial homeostasis10.1186/s13287-021-02656-41757-6512https://doaj.org/article/1be6bdaa122f4eaa98fa9e01194789de2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13287-021-02656-4https://doaj.org/toc/1757-6512Abstract Background PTEN-induced kinase 1 (PINK1) is a serine/threonine-protein kinase in mitochondria that is critical for mitochondrial quality control. PINK1 triggers mitophagy, a selective autophagy of mitochondria, and is involved in mitochondrial regeneration. Although increments of mitochondrial biogenesis and activity are known to be crucial during differentiation, data regarding the specific role of PINK1 in osteogenic maturation and bone remodeling are limited. Methods We adopted an ovariectomy model in female wildtype and Pink1 −/− mice. Ovariectomized mice were analyzed using micro-CT, H&E staining, Masson’s trichrome staining. RT-PCR, western blot, immunofluorescence, alkaline phosphatase, and alizarin red staining were performed to assess the expression of PINK1 and osteogenic markers in silencing of PINK1 MC3T3-E1 cells. Clinical relevance of PINK1 expression levels was determined via qRT-PCR analysis in normal and osteoporosis patients. Results A significant decrease in bone mass and collagen deposition was observed in the femurs of Pink1 −/− mice after ovariectomy. Ex vivo, differentiation of osteoblasts was inhibited upon Pink1 downregulation, accompanied by impaired mitochondrial homeostasis, increased mitochondrial reactive oxygen species production, and defects in mitochondrial calcium handling. Furthermore, PINK1 expression was reduced in bones from patients with osteoporosis, which supports the practical role of PINK1 in human bone disease. Conclusions In this study, we demonstrated that activation of PINK1 is a requisite in osteoblasts during differentiation, which is related to mitochondrial quality control and low reactive oxygen species production. Enhancing PINK1 activity might be a possible treatment target in bone diseases as it can promote a healthy pool of functional mitochondria in osteoblasts.So-Young LeeHyun-Ju AnJin Man KimMin-Ji SungDo Kyung KimHyung Kyung KimJongbeom OhHye Yun JeongYu Ho LeeTaeyoung YangJun Han KimHa Jeong LimSoonchul LeeBMCarticleMitochondriaOsteogenesisOsteoporosisPINK1Medicine (General)R5-920BiochemistryQD415-436ENStem Cell Research & Therapy, Vol 12, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mitochondria Osteogenesis Osteoporosis PINK1 Medicine (General) R5-920 Biochemistry QD415-436
spellingShingle	Mitochondria Osteogenesis Osteoporosis PINK1 Medicine (General) R5-920 Biochemistry QD415-436 So-Young Lee Hyun-Ju An Jin Man Kim Min-Ji Sung Do Kyung Kim Hyung Kyung Kim Jongbeom Oh Hye Yun Jeong Yu Ho Lee Taeyoung Yang Jun Han Kim Ha Jeong Lim Soonchul Lee PINK1 deficiency impairs osteoblast differentiation through aberrant mitochondrial homeostasis
description	Abstract Background PTEN-induced kinase 1 (PINK1) is a serine/threonine-protein kinase in mitochondria that is critical for mitochondrial quality control. PINK1 triggers mitophagy, a selective autophagy of mitochondria, and is involved in mitochondrial regeneration. Although increments of mitochondrial biogenesis and activity are known to be crucial during differentiation, data regarding the specific role of PINK1 in osteogenic maturation and bone remodeling are limited. Methods We adopted an ovariectomy model in female wildtype and Pink1 −/− mice. Ovariectomized mice were analyzed using micro-CT, H&E staining, Masson’s trichrome staining. RT-PCR, western blot, immunofluorescence, alkaline phosphatase, and alizarin red staining were performed to assess the expression of PINK1 and osteogenic markers in silencing of PINK1 MC3T3-E1 cells. Clinical relevance of PINK1 expression levels was determined via qRT-PCR analysis in normal and osteoporosis patients. Results A significant decrease in bone mass and collagen deposition was observed in the femurs of Pink1 −/− mice after ovariectomy. Ex vivo, differentiation of osteoblasts was inhibited upon Pink1 downregulation, accompanied by impaired mitochondrial homeostasis, increased mitochondrial reactive oxygen species production, and defects in mitochondrial calcium handling. Furthermore, PINK1 expression was reduced in bones from patients with osteoporosis, which supports the practical role of PINK1 in human bone disease. Conclusions In this study, we demonstrated that activation of PINK1 is a requisite in osteoblasts during differentiation, which is related to mitochondrial quality control and low reactive oxygen species production. Enhancing PINK1 activity might be a possible treatment target in bone diseases as it can promote a healthy pool of functional mitochondria in osteoblasts.
format	article
author	So-Young Lee Hyun-Ju An Jin Man Kim Min-Ji Sung Do Kyung Kim Hyung Kyung Kim Jongbeom Oh Hye Yun Jeong Yu Ho Lee Taeyoung Yang Jun Han Kim Ha Jeong Lim Soonchul Lee
author_facet	So-Young Lee Hyun-Ju An Jin Man Kim Min-Ji Sung Do Kyung Kim Hyung Kyung Kim Jongbeom Oh Hye Yun Jeong Yu Ho Lee Taeyoung Yang Jun Han Kim Ha Jeong Lim Soonchul Lee
author_sort	So-Young Lee
title	PINK1 deficiency impairs osteoblast differentiation through aberrant mitochondrial homeostasis
title_short	PINK1 deficiency impairs osteoblast differentiation through aberrant mitochondrial homeostasis
title_full	PINK1 deficiency impairs osteoblast differentiation through aberrant mitochondrial homeostasis
title_fullStr	PINK1 deficiency impairs osteoblast differentiation through aberrant mitochondrial homeostasis
title_full_unstemmed	PINK1 deficiency impairs osteoblast differentiation through aberrant mitochondrial homeostasis
title_sort	pink1 deficiency impairs osteoblast differentiation through aberrant mitochondrial homeostasis
publisher	BMC
publishDate	2021
url	https://doaj.org/article/1be6bdaa122f4eaa98fa9e01194789de
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PINK1 deficiency impairs osteoblast differentiation through aberrant mitochondrial homeostasis

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